Bottom Line:
Most of these RDVs resulted from recent retroduplications.In this study, we used the results of Phase 1 from the 1000 Genomes Project to investigate the variation in loss of ancestral (i.e. shared with other primates) retrocopies among different human populations.Altogether, we were able to detect 193 RDVs; the majority resulted from retrocopy deletion.

ABSTRACTGene retroposition leads to considerable genetic variation between individuals. Recent studies revealed the presence of at least 208 retroduplication variations (RDVs), a class of polymorphisms, in which a retrocopy is present or absent from individual genomes. Most of these RDVs resulted from recent retroduplications. In this study, we used the results of Phase 1 from the 1000 Genomes Project to investigate the variation in loss of ancestral (i.e. shared with other primates) retrocopies among different human populations. In addition, we examined retrocopy expression levels using RNA-Seq data derived from the Ilumina BodyMap project, as well as data from lymphoblastoid cell lines provided by the Geuvadis Consortium. We also developed a new approach to detect novel retrocopies absent from the reference human genome. We experimentally confirmed the existence of the detected retrocopies and determined their presence or absence in the human genomes of 17 different populations. Altogether, we were able to detect 193 RDVs; the majority resulted from retrocopy deletion. Most of these RDVs had not been previously reported. We experimentally confirmed the expression of 11 ancestral retrogenes that underwent deletion in certain individuals. The frequency of their deletion, with the exception of one retrogene, is very low. The expression, conservation and low rate of deletion of the remaining 10 retrocopies may suggest some functionality. Aside from the presence or absence of expressed retrocopies, we also searched for differences in retrocopy expression levels between populations, finding 9 retrogenes that undergo statistically significant differential expression.

Mentions:
With one exception (retro_hsap_88), all analyzed retrocopies are located in the introns of other genes; which is quite typical for retrocopies. Interestingly, retrogene located in the first intron of the zinc finger protein 761 gene (ZNF761), retro_hsap_2011 (annotated in the Gene database as TPM3P9), exapted the first exon of its host gene, according to annotations. This modification allowed the retrocopy to acquire a regulatory machinery, and consequently, the ability to be expressed, which we confirmed by standard PCR. In addition, part of the ZNF761 intron was incorporated as part of a retrogene exon (Fig 6). Another possible scenario is that a retrogene was incorporated into an existing two-exon splice variant. In any event, this retrocopy represents yet another example of the formation of new genes via retroposition followed by structural evolution [6, 22].

Mentions:
With one exception (retro_hsap_88), all analyzed retrocopies are located in the introns of other genes; which is quite typical for retrocopies. Interestingly, retrogene located in the first intron of the zinc finger protein 761 gene (ZNF761), retro_hsap_2011 (annotated in the Gene database as TPM3P9), exapted the first exon of its host gene, according to annotations. This modification allowed the retrocopy to acquire a regulatory machinery, and consequently, the ability to be expressed, which we confirmed by standard PCR. In addition, part of the ZNF761 intron was incorporated as part of a retrogene exon (Fig 6). Another possible scenario is that a retrogene was incorporated into an existing two-exon splice variant. In any event, this retrocopy represents yet another example of the formation of new genes via retroposition followed by structural evolution [6, 22].

Bottom Line:
Most of these RDVs resulted from recent retroduplications.In this study, we used the results of Phase 1 from the 1000 Genomes Project to investigate the variation in loss of ancestral (i.e. shared with other primates) retrocopies among different human populations.Altogether, we were able to detect 193 RDVs; the majority resulted from retrocopy deletion.

ABSTRACTGene retroposition leads to considerable genetic variation between individuals. Recent studies revealed the presence of at least 208 retroduplication variations (RDVs), a class of polymorphisms, in which a retrocopy is present or absent from individual genomes. Most of these RDVs resulted from recent retroduplications. In this study, we used the results of Phase 1 from the 1000 Genomes Project to investigate the variation in loss of ancestral (i.e. shared with other primates) retrocopies among different human populations. In addition, we examined retrocopy expression levels using RNA-Seq data derived from the Ilumina BodyMap project, as well as data from lymphoblastoid cell lines provided by the Geuvadis Consortium. We also developed a new approach to detect novel retrocopies absent from the reference human genome. We experimentally confirmed the existence of the detected retrocopies and determined their presence or absence in the human genomes of 17 different populations. Altogether, we were able to detect 193 RDVs; the majority resulted from retrocopy deletion. Most of these RDVs had not been previously reported. We experimentally confirmed the expression of 11 ancestral retrogenes that underwent deletion in certain individuals. The frequency of their deletion, with the exception of one retrogene, is very low. The expression, conservation and low rate of deletion of the remaining 10 retrocopies may suggest some functionality. Aside from the presence or absence of expressed retrocopies, we also searched for differences in retrocopy expression levels between populations, finding 9 retrogenes that undergo statistically significant differential expression.